Assessing the utility of the increased wall thickness score in diagnosing ATTR cardiomyopathy: a validation study

Abstract Introduction Cardiac amyloidosis due to transthyretin deposition (ATTR-CM) is often underdiagnosed. An increased left ventricular wall thickness (LVWT) should raise the suspicion for ATTR-CM, but it is a very frequent and non-specific finding. In order to improve diagnostic certainty, an echocardiographic score (Increased Wall Thickness [IWT] score) was recently proposed. The aim of our study was to assess the diagnostic performance of the IWT score in an independent population with increased LVWT. Methods We conducted a retrospective analysis of 295 consecutive patients studied at our centre for increased LVWT. All patients with severe aortic stenosis (AS) had ATTR-CM excluded by endomyocardial biopsy (EMB), during aortic valve replacement. ATTR-CM was considered as per the ESC algorithm. To be included, patients with Hypertrophic Cardiomyopathy (HCM) performed cardiac magnetic resonance and required a sarcomeric mutation for definite diagnosis. The echocardiographic IWT score was calculated for all patients, and categorized as certain (IWT≥8), unlikely (IWT ≤1) or indeterminate (1 < IWT < 8) for ATTR-CM diagnosis. Results A total of 295 patients were included (median age of 75 years [69-81], 61% men). Overall, 230 (70%) patients had hypertension and 164 (56%) chronic kidney disease (CKD). The median LVWT was 16 mm [IQR 15-19] and the median LVEF was 57% [IRQ 50-62%]. After diagnostic workup, 97 patients (33%) had confirmed ATTR-CM, 129 (44%) had isolated severe AS and 71 (24%) had hypertrophic cardiomyopathy (HCM). Fifteen patients had both severe AS and ATTR-CM. The median IWT score was 4 (IQR 2-7), with 21% of patients (n=64) showing an IWT score ≤1, 19% an IWT score ≥8, and 60% of patients (n=176) having an "indeterminate" value between 2 and 7. Despite this, on a continuous scale, the IWT showed good discriminative value (area under ROC curve 0.86, 95% 0.82-0.90, p<0.001). The criteria of IWT score ≥8 showed a positive predictive value of 82% (95% CI 72-89%), while an IWT score ≤ 1 yielded a negative predictive value of 92% (95% CI 84-97%) - Figure. Conclusions Even though the IWT score provides "indeterminate" results in a large proportion of patients, values at the ends of the spectrum showed good negative and positive predictive values for the diagnosis of ATTR-CM. Our findings provide external validation for this echocardiographic score, and support its use in the diagnostic workup of patients with increased wall thickness and suspected ATTR-CM.